1. Field of the Invention
The present invention relates to hyperthermia, which is the use of heat to selectively destroy cancer cells, and more particularly to a technique for obtaining field homogeneity in hyperthermia.
2. Description of the Prior Art
Hyperthermia has become one of the most rapidly growing areas of cancer research. Methods that are presently in use either involve applications of heat to the entire body of a patient or applications of heat to a selective portion of the body of the patient. When the method of selective applications of heat is used, the heat is generated by conversion of either ultrasonic energy or microwave energy within the tissue itself.
U.S. Pat. No. 4,069,827, entitled Diathermy Apparatus, issued to Francis I. Dominy on Jan. 24, 1978, teaches a combination for use with a diathermy apparatus which includes an oscillator that includes a controlled conduction device having a pair of output electrodes and a device for controlling the controlled conduction device in response to a reference voltage for a particular voltage level.
U.S. Pat. No. 4,016,886, entitled Method for Localizing Heating in Tumor Tissue, issued to James D. Doss and Charles W. McCabe on Apr. 12, 1977, teaches a method of treating tumorous tissue in situ which includes heating substantially only the tumorous tissue by placing at least two electrodes in operative relationship, passing radiofrequency current having a frequency less than 1 MHz substantially directly through the tumorous tissue and forming and placing electrodes to shape the field of the radiofrequency current by inserting into the patient's body a plurality of electrically conductive pins on either side of the tumorous tissue with the distance between opposite pins being inversely proportional to the required radiofrequency field intensity and current. The method also includes electrically interconnecting the pins on one side of the tumorous tissue and electrically interconnecting the pins on the other side of the tumorous tissue. The method further includes applying the radiofrequency current to the interconnected pins on both sides of the tumorous tissue.
There have been problems in obtaining uniform heating when microwave and radiofrequency fields are used. In an article, entitled "Therapeutic Applications of Electromagnetic Power," published in the Proceedings of the I.E.E.E., January, 1974, pages 55 to 75, the authors, Arthur W. Guy, Justus F. Lehmann and Jerry B. Stonebridge, discuss diathermy ". . . which is a technique used for producing therapeutic heating in tissue by conversion of physical forms of energy such as ultrasound, EM shortwaves, or microwaves into heat after being transmitted transcutaneously to deep afflicted tissue areas. The technique has been used in physical medicine from the time that the physical energy sources have been available to man." The article traces the history of the use of electromagnetic waves through today's present use of the microwave frequencies of 2450 megahertz and of 915 megahertz in therapeutic uses. The three inch (3") wavelength of the 2450 megahertz microwaves allows directionality thereof, but it is not short enough to allow it to be focused within the body. In order to focus microwave energy to the dimensions in the range of centimeters, the frequency of the microwaves must be in the range of 50,000 to 75,000 megahertz. Although little work has been done in this range of frequencies, it would appear that the attenuation of these microwaves would result in poor penetration into the tissue. There have been reports which indicate that the microwave of a 2450 megahertz frequency can give rise to hot spots in an area a short distance away from a fat-muscle interface which are due to a standing wave effects. These standing waves are not seen if the microwaves of a 915 megahertz frequency are used.
In their paper, entitled "Prediction of Dynamic Temperature Distribution in Normal and Neoplastic Tissues During Diathermy," presented at the 30th Annual Conference for Engineering in Medicine and Biology (30th ACEMB), held in Los Angeles, Calif. on Nov. 5 through 9, 1977, H. P. Stein and R. K. Jain stated:
"Hyperthermia is destructive to cancer cells above 40.degree. C. and is lethal to normal cells of the host tissue at a temperature above 42.degree. C. It is equally harmful in the temperature range of 37.5.degree. C. to 40.degree. C. where metabolism of the tumor cells is progressively increased. Due to this narrow range of operation, a definite need exists to quantify and predict the temperature distribution in the neoplastic and surrounding normal tissues of the host to exploit hyperthermia for the optimal management of cancer."
In their paper, entitled "Clinical Applications of Hyperthermia Techniques in Cancer," also presented at the 30th ACEMB, C. J. Sternhagen, J. M. Larkin, J. D. Doss, P. W. Day, S. Edwards and D. E. Smith stated:
"Localized current field techniques using 500 kilohertz radiofrequency current have been used in oral cavity and other accessible malignancies. This frequency has the advantage of allowing the physician to continuously monitor the temperature by the use of surface thermistors as well as thermistors placed directly into the tumor or adjacent normal tissue. Continuous monitoring of the treatment temperature has been one of the criteria of clinical protocols used, and appears to be essential to developing the hyperthermia techniques while maintaining patient safety--because great variations of temperatures occur at times at ranges within a few millimeters. The first localized hyperthermia technique used in human patients in this series was basically a non-invasive technique involving the use of electrode plates placed so that the most hypoxic portion of the malignancies would receive the highest temperature in the treatment volume, while normal structures would be relatively spared by receiving a lower temperature. This has the advantage of delivering the heat where the tumor is most likely to be resistant to radiation treatment: the hypoxic center of the tumor. It has the disadvantage of being somewhat less capable of delivering a homogenous hyperthermia treatment to deeper tumor structures. Another localized hyperthermia technique used consisted in the placement of needles in an invasive biplanar interstitial implant configuration. The needles are placed surrounding the tumor in two parallel rows with the control thermistor and monitor thermistors arrayed appropriately between the rows of needles. Using these localized methods a treatment can be maintained for periods up to thirty minutes during which the temperature will fluctuate less than one degree centigrade [(1.degree. C.)]. This is usual treatment time currently in use. The temperature currently in use is in the range of 42 to 44 degrees C., with shorter durations of heating employed if the temperature approaches the higher range."
Hyperthermia is often used in synergism with ionizing radiation to produce cell destruction which is selective toward cancer cells. When hyperthermia of the whole body mode is used, the only selectivity is the differential response of cancer cells to an elevated temperature. However, when hyperthermia of the local heating mode is used, the object is to produce a temperature rise of one degree to four degrees Centigrade (1.degree. to 4.degree. C.) at the site of the cancer cells. Local hyperthermia is usually produced by absorption of either ultrasonic energy or electromagnetic energy and its conversion to heat within the tissue. When either source of energy is used, consideration must be given to the design of the applicator and the interaction between the electromagnetic or ultrasonic field and the tissue so that uniform heating is obtained in the desired region of application with minimal insult to other tissues.
Some of the solutions to the problems which are associated with induced hyperthermia through interstitially implanted electrodes have been attempted with varying degrees of success. Several of these techniques are: (1) reducing current density by using lower power; (2) increasing the contact area by the use of more needles; (3) actively cooling the electrodes; and (4) using some other configuration of electrodes.
The University of Arizona Medical Center is perhaps the medical center with the greatest experience in the utilization of interstitially implanted electrodes for the induction of localized hyperthermia. Although the results have been admirable and overall encouraging, some unexpected morbidity has been experienced in some of the treated animals which is attributable to localized "hot spots." At present there are satisfactory methods of avoiding "hot spots" including those listed above. The first technique could result in reduced effectiveness of induced hyperthermia, and, if the tumor temperature does not at least reach 41.5.degree. C., result even in a possible enhancement of tumor growth. The utilization of the second technique could result in a less than optimum tumor radiation dose if the needles are implanted too close together in order to increase the contact area for hyperthermia treatment (unless non-radioactive needles are interdispersed with radioactive ones). The third technique is impractical for an interstitial implant except for that region of the implanted needle protruding from the skin. The fourth technique has not been developed until the present invention.